Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NO, a simple molecule synthesized from L-arginine by NO synthases, has been identified to play an important role in cell communication, cell defense and cell injury. The half life of NO is very short because NO either reacts with superoxide anion (O2-), and/or binds to heme molecules or Fe-S groups present in proteins. The biological effects of NO depend on both the concentration of NO at the site of action as well as upon the specific location where NO is generated. Small quantities of NO are generated by cNOS such as that present in the vascular endothelium, while large quantities of nitric oxide are synthesized by iNOS in response to cytokines or bacterial products. Within the kidney NO generated by endothelial cNOS participates in the regulation of the glomerular microcirculation by modifying the tone of the afferent arteriole and mesangial cells (Fig. 4). In addition, NO generated by macula densa and the afferent arteriole control glomerular hemodynamics via TGF and by modulating renin release. Therefore NO is important in the physiologic regulation of glomerular capillary blood pressure, glomerular plasma flow and the glomerular ultrafiltration coefficient. Through its actions on glomerular pressures and flows, NO may also regulate the macro- and micromolecular traffic through the mesangium. Chronic NO insufficiency causes hypertension and glomerular damage and may be causally involved in the genesis of salt dependent hypertension. Increased NO production may be involved in the early pathogenic hemodynamic changes in diabetes and in the physiologic hemodynamic responses to normal pregnancy. Maintenance of the antithrombogenic properties of the endothelium is another important action of NO which inhibits platelet aggregation and adhesion. Large quantities of NO such as that synthesized by either glomerular cells or macrophages during glomerular inflammation may lead to glomerular injury. A better understanding of the physiology and pathophysiology of NO in the kidney will lead to the development of new therapeutic avenues.
 ...
PMID:Glomerular actions of nitric oxide. 756 80

Progression of diabetic nephropathy is now associated with intrarenal hemodynamic disorders (renal hyperperfusion, hyperfiltration, intraglomerular hypertension). The cause of these disorders is unclear. It is supposed that the relaxation factor which is produced by the vascular endothelium (endothelial relaxation factor-ERF) and an endogenous nitrogen oxide (NO) can cause the above intrarenal hemodynamic alterations in diabetes mellitus. The production of ERF/NO in 35 patients with insulin-dependent diabetes mellitus who had varying severities of diabetic nephropathies were examined. These included the following groups: 1) patients without diabetic nephropathy (n = 9); 2) those with incipient diabetes mellitus (n = 12), 3) those with severe diabetes mellitus (n = 14). From groups 1 and 2, 5 patients with hyperfiltration were identified, their glomerular filtration rate were more than 140 ml/ml. The ability of the cells to produce ERF/NO was indirectly estimated, by determining the levels of human platelet guanylate cyclase in the presence of L-arginine, a NO precursor, the accumulation of cGMP in the cells and plasma. When L-arginine was present, the activity of guanylate cyclase was virtually unchanged in Group 1, but it was substantially increased in Groups 2 and 3, by reaching its peak in patients with hyperfiltration (Group 4). The platelet and plasma levels of cGMP corresponded to the enhancement of guanylate cyclase activity in the presence of L-arginine and increased as diabetic nephropathy progressed. Thus, it is suggested that there is ERF/NO hyperproduction in patients at a high risk for diabetic nephropathy (those having hyperfiltration). ERF/NO is likely to promote the dilation of glomerular arterioles, which results in the development of hyperfiltration and intraglomerular hypertension, causing diabetic nephropathy progression.
 ...
PMID:[Endothelial relaxation factor in the development of diabetic nephropathy]. 762 82

Neutral endopeptidase 24.11, a membrane-bound metallopeptidase, cleaves, and degrades vasoactive peptides such as atrial natriuretic peptide, endothelin, angiotensin I, substance P, and bradykinin. Therefore, the presence of this metallopeptidase may contribute to the regulation of vascular tone and local inflammatory responses in the vascular endothelium and elsewhere. We determined neutral endopeptidase in cultured human endothelial cells from different vascular beds and studied its regulation by protein kinase C. Neutral endopeptidase was detected in all cultured endothelial cell types. Lowest concentrations were measured in human endothelial cells from umbilical veins (360 +/- 14 pg/mg protein), followed by pulmonary and coronary arteries; higher concentrations were found in endothelial cells from the cardiac microcirculation (1099 +/- 73 pg/mg protein). Neutral endopeptidase content increased during cell growth but was not affected by endothelial cell growth factor or modifications of the growth medium. Stimulation of protein kinase C with 1-oleoyl-2-acetyl-rac-glycerol (0.1 to 1 mumol/L) and phorbol 12-myristate 13-acetate (0.01 to 0.1 mumol/L) induced a time- and concentration-dependent increase of endothelial cells that was inhibited by cycloheximide (5 mumol/L), an inhibitor of protein synthesis. Incubation with phospholipase C (1 mumol/L) and thrombin (10 IU/mL) induced upregulation of neutral endopeptidase, resulting in 158 +/- 26% and 150 +/- 22% increases, respectively, compared with controls. The thrombin effect was inhibited by calphostin C (1 mumol/L), an inhibitor of protein kinase C. Endothelial neutral endopeptidase is constitutively expressed in endothelial cells from different origins and is inducible by thrombin via activation of the protein kinase C pathway.
Hypertension 1995 Aug
PMID:Regulation and differential expression of neutral endopeptidase 24.11 in human endothelial cells. 763 30

The seronin or 5-hydroxytryptamine (5-HT) is a biogenic amine involved in diverse physiologic and physiopathological processes in the cardiovascular system. 5-HT may lower the arterial blood pressure by an action on central 5-HT1A receptors, or may increase it by stimulation of 5-HT2 receptors located in vascular smooth muscle. It has been postulated that hypofunction of 5-HT1A receptors, or the exaggerated stimulation of 5-HT2 receptor may be associated with arterial hypertension and that agonists of the first type (indorenate or 8-OH-DPAT) or antagonists of the second type (ketanserin or pelanserin) allow the control of arterial hypertension. On the other land, ketanserin and pelanserin attenuated the hemodynamic manifestations in an experimental model of thromboembolism, suggesting that 5-HT is involved in such phenomenon. Finally, 5-HT could be related with the presence of angor pectoris during hypertension or atherosclerosis, diseases that are associated with a lesional of the vascular endothelium, a condition that favors the 5-HT induced vasoconstriction in coronary arteries.
 ...
PMID:[Serotoninergic receptors and cardiovascular diseases]. 765 75

Microcystin (Mcyst) and calyculin A (CalA) in vitro inhibit protein phosphatases (PP)1 and 2A activity (IC50 0.1-2.0 nM). This study was aimed at determining the contribution of PP inhibition to Mcyst hepatotoxicity by comparing the effect of these two chemically different inhibitors in perfused rat livers. Both compounds (60 micrograms Mcyst and 6 micrograms CalA/150 ml perfusate) caused cessation of bile flow and inhibition of PP activity after 20 min of perfusion to 8% and 37% of control activity for Mcyst and CalA treatments, respectively. Histopathological findings included loss of cord sinusoidal pattern and of normal liver architecture. There also was hepatocyte swelling, pyknotic changes and necrosis. Mcyst caused a modest increase in perfusion pressure of 1.2 cm of water, whereas CalA caused a 3-fold increase. The most likely explanation for this hemodynamic effect is direct action of CalA on the vascular endothelium and/or sinusoidal and perisinusoidal cells. This possibility was explored with hepatocytes and sinusoidal endothelial cells. PP activity of both cell types was inhibited by 10 to 100 nM CalA followed later by cell lysis, whereas Mcyst (500 nM-2 microM) had no effect on sinusoidal endothelial cells, but inhibited PP activity and caused later lysis in hepatocytes (Mcyst 20-160 nM). Mcyst hepatotoxicity is therefore a direct consequence of PP inhibition in hepatocytes, the loss of sinusoidal integrity following from the primary toxic insult to the hepatocyte. Inhibition of PP activity of the cells of the presinusoidal vasculature and/or nonparenchymal cells results in hepatic hypertension.
 ...
PMID:Differential toxicity of the protein phosphatase inhibitors microcystin and calyculin A. 771 10

We previously showed that endothelin-1 expression was increased in vascular endothelium of deoxycorticosterone acetate-salt hypertensive rats, whereas in spontaneously hypertensive rats (SHR) it is similar to or less than that in normotensive rats. Treatment with the combined endothelin type A/endothelin type B receptor antagonist bosentan moderately reduced blood pressure rise and nearly completely blunted the development of vascular hypertrophy, particularly in small arteries, in the deoxycorticosterone acetate-salt hypertensive model, suggesting a paracrine role for vascular endothelin-1 in the induction of blood vessel hypertrophy in some forms of experimental hypertension. In the present study we examined the effect of chronic oral treatment for 4 weeks of 12-week-old SHR and Wistar-Kyoto rats (WKY) with 100 mg/kg per day bosentan. Blood pressure rose to hypertensive levels similarly in bosentan-treated and untreated SHR; systolic pressure of WKY was also unaffected. The wet weights of the heart, of aortic segments, and of the mesenteric arterial bed were similar in treated and untreated SHR. When coronary, renal arcuate, mesenteric, and femoral small arteries were evaluated on a wire myograph, the media width and media-to-lumen ratio were greater and the lumen diameter was smaller in vessels from SHR relative to those from WKY, except in small arteries from the renal cortex, in which the lumen was not significantly different in both strains. The media cross-sectional area of small arteries fom the four vascular beds was similar in both strains. Identical morphometric parameters were found in the four vascular beds in bosentan-treated and untreated rats of eh strain.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Effect of chronic treatment of adult spontaneously hypertensive rats with an endothelin receptor antagonist. 772 89

We examined the regulatory influence of nitric oxide on development of calcium- and protein kinase C-dependent basal tone in rings of thoracic aortas from rats with aortic coarctation-induced hypertension and from normotensive controls. Aortic rings from hypertensive rats but not those from normotensive rats, bathed in Krebs' bicarbonate buffer and subjected to 2 g of passive stretch, were relaxed by removal of calcium from the buffer and by the protein kinase C inhibitors staurosporine and calphostin C. Protein kinase C activity was much greater in homogenates of aortae from hypertensive rats than in those from normotensive controls (2124 +/- 785 versus 608 +/- 73 pmol.min-1.mg protein-1, respectively). Relaxant responses to removal of calcium and to staurosporine were greater in aortic rings rubbed to remove the vascular endothelium than in endothelium-intact rings (-1.07 +/- 0.12 versus -0.70 +/- 0.10 g tension/mg tissue, respectively, for calcium removal and -1.10 +/- 0.12 versus -0.65 +/- 0.08 g tension/mg tissue, respectively, for staurosporine). Treatment with an inhibitor of nitric oxide synthesis increased calcium-dependent tone in both intact and endothelium-denuded aortic rings from hypertensive rats. Conversely, the administration of sodium nitroprusside or L-arginine reversed tone in both intact and denuded aortic rings from hypertensive rats, but acetylcholine reversed tone only in intact rings. The relaxant effects of these agents were paralleled by increases in cyclic guanosine monophosphate in aortic tissue. We conclude that aortic rings from rats with aortic coarctation-induced hypertension display calcium-dependent, protein kinase C-mediated tone in the absence of exogenous vasoconstrictors.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Calcium- and protein kinase C-dependent basal tone in the aorta of hypertensive rats. 772 28

Hypertension is thought to alter many of the functions of the vascular endothelium. The present study examines whether shear stress-induced endothelium-dependent skeletal muscle arteriolar dilation is compromised in genetically hypertensive rats. Changes in the diameter of isolated, perfused arterioles (approximately 60 microns) from gracilis muscles of 12-week-old normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR) were investigated. At a constant perfusion pressure (80 mm Hg), the active diameter of NWR and SHR arterioles was 57.1 +/- 2.0 and 50.9 +/- 3.5 microns, respectively (mean +/- SEM), while the passive diameter (in Ca(2+)-free solution) was 113.2 +/- 3.1 and 100.6 +/- 2.9 microns, respectively. Increases in wall shear stress (from 0 to 100 dyne/cm2) elicited by increases in perfusate flow (from 0 to 25 microL/min) resulted in marked increases in the diameter of NWR arterioles, but such increases produced substantially smaller dilations in SHR arterioles (43.0 versus 18.9 microns). The prostaglandin synthesis inhibitor indomethacin (10(-5) mol/L) significantly attenuated the shear stress-induced dilations in both strains of rats. In contrast, the nitric oxide synthase inhibitor N omega-nitro-L-arginine (10(-4) mol/L) significantly shifted the shear stress-diameter curve to the right in vessels from NWR (by 50 dyne/cm2) but not in those from SHR. Thus, in gracilis muscle arterioles of SHR, the reduced dilation to increases in shear stress seems to be due to the lack of nitric oxide synthesis and/or release in response to shear stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Shear stress-induced dilation is attenuated in skeletal muscle arterioles of hypertensive rats. 772 29

In a group of neonatal piglets an increase in pulmonary arterial pressure was obtained within 2 weeks after a partial mechanical obstruction of the left atrium by a balloon catheter. Mean pulmonary artery pressure in the hypertensive animals (n = 6) was 24 +/- 2 mm Hg as compared (p < 0.01) with 15 +/- 1 mm Hg in controls (n = 6) or 9 +/- 2 mm Hg in sham-operated piglets (n = 6). Cardiac index was reduced in hypertensive versus control and sham groups: 0.15 +/- 0.01 versus 0.32 +/- 0.05 and 0.29 +/- 0.04 L.min-1.kg-1 (p < 0.05), respectively. There was no detectable difference on histologic examination in the pulmonary arteries between the three groups. Right ventricular hypertrophy was observed in the group with pulmonary hypertension. In hypertensive piglets, isolated conduit pulmonary arteries did not relax when stimulated with acetylcholine; they always relaxed to sodium nitroprusside. These data suggest that the first stages of perturbations reported during pulmonary venous hypertension occur at the level of the pulmonary vascular endothelium. This neonatal model of pulmonary hypertension is simple to perform and might be useful for further investigations.
 ...
PMID:Endothelial dysfunction in venous pulmonary hypertension in the neonatal piglet. 773 12

The study examined the effect of salt-induced hypertension on vascular relaxation in response to magnesium sulphate during pregnancy. Pregnant Wistar rats were fed for 6 weeks on a diet containing 0.3% (control) and 8.0% (test) sodium chloride. Aortic rings were then removed and contracted with 10(-7) M phenylephrine or 30 mM potassium chloride. High salt intake increased the systolic blood pressure of the rats and increased the relaxation of phenylephrine-contracted intact rings in response to magnesium sulphate. Neither endothelium removal nor treatment with 10(-6) M indomethacin altered the relaxation of rings from the two groups of rats, when contracted with potassium chloride. Both processes significantly (P < 0.05) and similarly decreased the sensitivity and the maximal relaxation of rings from test rats contracted with phenylephrine; the relaxation of rings from the control rats was not altered. The results suggest that the relaxation of isolated rat aortic rings contracted with phenylephrine is enhanced in pregnant rats with salt-induced hypertension. The mechanism involved in this enhancement is dependent on the vascular endothelium and receptor activation, and is indomethacin sensitive.
 ...
PMID:The mechanism of relaxation in response to magnesium by the aorta of pregnant rats with salt-induced hypertension. 773 40


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>